Orally administered therapeutic agents are rapidly transported to the stomach and small intestine for absorption across gastro-intestinal mucosal membranes into the blood. The efficiency of absorption of a therapeutic agent (i.e. the ratio of the amount entering the blood to the amount administered) following oral administration of many drugs can be low because of several factors which serve to metabolize the administered chemical. Low absorption efficiency is particularly problematic with polypeptide therapeutic agents.
The gastrointestinal tract secretes a variety of agents that metabolize polypeptides. Exemplary of such catabolic agents are pepsin, trypsin, chymotrypsin, carboxypolypeptidases, aminopolypeptidases and dipeptidases. Polypeptides that escape catabolism in the stomach and small intestine are transported across the cells lining the gastrointestinal tract into the portal circulation, which carries absorbed polypeptides to the liver. Absorbed polypeptides are subject to further degradation by a myriad of hepatic metabolic events. Such hepatic degradation of absorbed materials from the blood before such materials enter the general systemic circulation is known in the pharmaceutical art as the "first pass effect".
As a result of these factors causing low absorptive efficiency of orally administered therapeutic agents, particularly polypeptides, if the choice of the route of administration is the oral route, it is necessary to administer large dosages of such polypeptides. This is costly in many cases and inefficient. Alternatively, such therapeutic agents can be administered via other routes such as intravenously, subcutaneously or intraperitoneally. These alternate routes are all invasive by nature and can involve pain and discomfort to a subject. There is, therefore, a pressing need for new, efficient, cost-effective and non-invasive methods and compositions for the administration to patients of therapeutic agents which would be otherwise degraded if administered orally.
The present invention provides novel compositions and methods for the sublingual administration of therapeutic agents.